DESCRIPTION (Verbatim from the applicant's abstract): Sight is critically dependent on the development of appropriate eye morphology and cell types. Although many genes involved in eye development have been isolated, the genetic regulatory pathways that control vertebrate retinal cell differentiation remain undetermined. Moreover, the link between gene activity and cell determination is not well understood. This proposal aims to investigate the cellular and molecular mechanisms of eye formation by (1) decifering the functional relationships among the different genes that control eye formation and then (2) characterizing the role of two retinal genes integral to eye development, Chx10 and Mitf or microphthalmia. By analyzing the expression patterns of the eye transcription factors in wild-type embryos and embryos over-expressing the individual genes, it will be possible to outline a genetic hierarchy. Dominant-negative inhibition and enhancer activation of their function in the developing animal will be used to more precisely define the functional relationships of these genes. In addition, over-expression or inhibition of Chx10 and Mitf at the 2-cell stage and in embryonic optic vesicles (stage 18) may reveal new functions for these genes that previous studies in mice have not.